Bimatoprost, (5Z)-7-[(1R,2R,3R,5S)-3,5-Dihydroxy-2-[1E,3S)-3-hydroxy-5-phenyl-1-pentenyl]cyclopentyl]-5-N-ethylheptenamide, is a synthetic derivative of prostaglandin PGF2. It is indicated for intraocular pressure regulation and treatment of open angle glaucoma, and is available from the innovator Allergan, Inc. as LUMIGAN®.

The (S)-I intermediate, (1S,5R,6R,7R)-6-[(3S)-3-hydroxy-5-phenyl-1-pentenyl]-7-[(4-benzoyl)oxy]-2-oxabicyclo[3,3,0]octan-3-one,
compound (S)-I, is one of a pair of epimers, and, thus, differs in configuration from the corresponding (R)-I compound, (1S,5R,6R,7R)-6-[(3R)-3-hydroxy-5-phenyl-1-pentenyl]-7-[(4-benzoyl)oxy]-2-oxabicyclo[3,3,0]octan-3-one,
compound (R)-I, at only one asymmetric carbon, the carbon at the 3 position.
In the preparation of bimatoprost, only the (S)-I intermediate, leads to the active form of the drug. In one example, U.S. Pat. No. 3,969,396 discloses the following process for the synthesis of bimatoprost:

There are a number of methods used to obtain the required stereochemistry, such as by chromatography and crystallization. Currently, the most widely practiced method of separation of diastereomeric mixtures in the case of the (S)-I intermediate is via chromatography. However, this stereoselective synthesis is still an unfavorable process for scale up due to its multi-step nature and cost. The difficulty in chromatographic separation stems from the fact that the two epimers do not differ greatly in their affinity, and, thus, their retention times are too close to allow efficient separation in one chromatographic step, especially on large scale. Therefore, a process for the separation of the (S)-I intermediate from a mixture of the epimers is highly desirable. The present invention provides such a process by greatly improving the efficacy of chromatographic separation.